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首页> 外文期刊>Genome >Extended longevity and survivorship during amino-acid starvation in a Drosophila Sir2 mutant heterozygote
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Extended longevity and survivorship during amino-acid starvation in a Drosophila Sir2 mutant heterozygote

机译：果蝇Sir2突变杂合子中的氨基酸饥饿期间延长的寿命和生存期。

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摘要

The regulation of energy homeostasis is pivotal to survive periods of inadequate nutrition. A combination of intricate pathways and proteins are responsible for maximizing longevity during such conditions. The sirtuin deacetylase Sir2 is well conserved from single-celled yeast to mammals, and it controls a number of downstream targets that are active during periods of extreme stress. Overexpression of Sir2 has been established to enhance survival of a number of model organisms undergoing calorie restriction, during which insulin receptor signalling (IRS) is reduced, a condition that itself can enhance survivorship during starvation. Increased Sir2 expression and reduced IRS result in an increase in the activity of the transcription factor foxo, an advantageous activation during stress but lethal when overly active. We have found that a lowered gene dosage of Sir2, in mutant heterozygotes, can extend normal longevity and greatly augment survivorship during amino-acid starvation in Drosophila. Additionally, these mutants, in either heterozygous or homozygous form, do not appear to have any disadvantageous effects upon development or cell growth of the organism unlike IRS mutants. These results may advance the understanding of the biological response to starvation and allow for the development of a model organism to mimic the ability of individuals to tolerate nutrient deprivation.
机译：能量稳态的调节对于营养不足的生存至关重要。在这种情况下，复杂的途径和蛋白质的结合将使寿命最大化。沉默调节蛋白的脱乙酰基酶Sir2从单细胞酵母到哺乳动物都非常保守，并且它控制着许多在极端压力下活跃的下游靶标。已经建立了Sir2的过表达，以增强遭受卡路里限制的许多模型生物的生存，在此过程中，胰岛素受体信号传导（IRS）减少，这种状况本身可以提高饥饿期间的存活率。 Sir2表达的增加和IRS的减少会导致转录因子foxo的活性增加，这在压力下是一种有利的激活，但是在过度活跃时会致命。我们已经发现，在突变杂合子中降低Sir2基因的剂量可以延长果蝇的氨基酸饥饿期间的正常寿命并大大提高其存活率。另外，与IRS突变体不同，这些杂合体或纯合体形式的突变体似乎对生物体的发育或细胞生长没有不利影响。这些结果可以促进对饥饿的生物学反应的理解，并允许模型生物的发展来模拟个体耐受营养剥夺的能力。

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